Virological characteristics of SARS-CoV-2 Omicron BA.5.2.48

Front Immunol. 2024 Oct 1:15:1427284. doi: 10.3389/fimmu.2024.1427284. eCollection 2024.

Abstract

With the prevalence of sequentially-emerged sublineages including BA.1, BA.2 and BA.5, SARS-CoV-2 Omicron infection has transformed into a regional epidemic disease. As a sublineage of BA.5, the BA.5.2.48 outbroke and evolved into multi-subvariants in China without clearly established virological characteristics. Here, we evaluated the virological characteristics of two isolates of the prevalent BA.5.2.48 subvariant, DY.2 and DY.1.1 (a subvariant of DY.1). Compared to the normal BA.5 spike, the double-mutated DY.1.1 spike demonstrates efficient cleavage, reduced fusogenicity and higher hACE2 binding affinity. BA.5.2.48 demonstrated enhanced airborne transmission capacity than BA.2 in hamsters. The pathogenicity of BA.5.2.48 is greater than BA.2, as revealed in Omicron-lethal H11-K18-hACE2 rodents. In both naïve and convalescent hamsters, DY.1.1 shows stronger fitness than DY.2 in hamster turbinates. Thus regional outbreaking of BA.5.2.48 promotes the multidirectional evolution of its subvariants, gaining either enhanced pathogenicity or a fitness in upper airways which is associated with higher transmission.

Keywords: BA.5; Omicron; SARS-CoV-2; animal models; pathogenicity; spike.

MeSH terms

  • Angiotensin-Converting Enzyme 2 / genetics
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Animals
  • COVID-19* / immunology
  • COVID-19* / transmission
  • COVID-19* / virology
  • China / epidemiology
  • Cricetinae
  • Humans
  • Mesocricetus
  • Mutation
  • SARS-CoV-2* / genetics
  • SARS-CoV-2* / pathogenicity
  • SARS-CoV-2* / physiology
  • Spike Glycoprotein, Coronavirus* / genetics
  • Spike Glycoprotein, Coronavirus* / immunology
  • Spike Glycoprotein, Coronavirus* / metabolism

Substances

  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Angiotensin-Converting Enzyme 2

Supplementary concepts

  • SARS-CoV-2 variants

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work is supported by the National Key Research and Development Program of China (2023YFC0871100 to YWG, 2021YFC2302405 to XW, 2021YFF0702500 to JL and 2023YFC2605500 to QC). This work is also supported by the Natural Science Foundation of Jiangsu Province (BE2019730) and Medical Research Project of Jiangsu Provincial Health Commission (Z2023003) to WZ.